IgA is the major immunoglobulin in the secretions and is important in mucosal defense. Although secretion of IgA is highly dependent on T cells, the specific regulatory mechanisms involved are not completely understood. The proposed research is designed to examine the T cell influences on the proliferation and differentiation of the precursors of IgA secreting cells. Mitogen stimulated normal human peripheral blood T cells produce culture supernatants which augment IgA secretion of peripheral blood B cells and IgA secreting EBV transformed B cell clones. However, the action of these crude T cell supernatants is not specific for IgA. The proposed research will attempt to isolate the specific T cell factor(s) responsible for the IgA augmentation induced and characterize the T cells producing such factors. T cell supernatant and the isolated T cell factors will then be utilized to characterize the IgA response of peripheral blood and tissue B cells and B cell clones. B cells will be separated into subpopulations on the basis of surface immunoglobulin isotype and expression of activation antigens to determine those steps in the differentiation of IgA secreting cells that are influenced by T cells. The role of T cell influences in the promotion of an isotype switch to IgA will also be examined. Results obtained from these studies will then be utilized to examine tissue differences in IgA secretion and the specific defects in individuals with IgA deficiency. A better understanding of the regulation of the differentiation of IgA secreting cells is of major importance in defining the immunologic mechanisms involved in mucosal immunity and derangements predisposing to gastrointestinal disease, an area of primary concern to the applicant. The availability of Dr. Lipsky's expertise in B cell differentiation should provide the ideal environment to complete this work.